The long-term objective of this proposal is to develop a practical method for inactivating viruses in a blood-derived product, intravenous immunoglobulin (IVIG), that is applicable to the manufacturing setting. The method represents a significant commercial opportunity for treating plasma derivatives contaminated with pathogenic viruses like HIV, hepatitis C (HCV), hepatitis A (HAV) and parvovirus Bl9. Non-enveloped viruses like parvovirus Bl9 and HAV are quite resistant to a variety of physical and chemical inactivation procedures. viral inactivation is achieved by a novel class of agents, INACTINE(TM) compounds, that are highly selective for nucleic acid over proteins or other biomolecules. Preliminary results have established that these compounds can inactivate viruses at up to 3 log10/hr and are effective against both enveloped and non-enveloped viruses. In this proposal, a series of INACTINE(TM) compounds will be screened and the most active one selected for optimization of inactivation in IVIG. inactivation kinetics will be defined for HIV and for model viruses for human parvovirus Bl9 and HCV. Physical and biological properties of IVIG will be analyzed under optimal conditions for viral inactivation. This research will set the stage for a me comprehensive program to develop an effective and practical product, with Phase II SBIR support. PROPOSED COMMERCIAL APPLICATION: INACTINE(TM) compounds will be useful for inactivating pathogenic viruses in plasma derivatives in a manufacturing setting. The method will be developed first with IVIG and then applied to other derivatives. Current information indicates that the cost of manufacture of INACTINE(TM) lends itself to very cost-effective use of the technology.